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Id: biblio-1001591
Autor: Fattahi, Ali; Ghiasi, Mansoureh; Mohammadi, Pardis; Hosseinzadeh, Leila; Adibkia, Khosro; Mohammadi, Ghobad.
Título: Preparation and physicochemical characterization of prazosin conjugated PLGA nanoparticles for drug delivery of flutamide
Fonte: Braz. J. Pharm. Sci. (Online);54(4):e17228, 2018. tab, graf.
Idioma: en.
Resumo: In the current work, a sustained drug delivery system of flutamide (FLT) was developed using Poly(D,L-lactide-co-glycolide) (PLGA) decorated bypoly(ethylene glycol) (PEG) grafted prazosin (PLGA-PEG-Praz) as a targeting moiety. In a multi-step reaction, PLGA was linked to PEG and prazosin. The structure of the synthesized polymers was confirmed by FTIR and 1H-NMR. Flutamide-loaded nanoparticles were prepared by quasi-emulsion solvent diffusion technique. The nanoparticles were evaluated for size, zeta potential, polydispersity index, drug crystallinity, loading efficiency, and release properties. Also, the physicochemical properties of the nanoparticles were analyzed using Scanning Electron Microscopy (SEM), Differential Scanning Calorimetry, and Powder X-Ray Diffractometry (XRD). The particle size of nanoparticles was ranged between 191 and 249 nm. Loading efficiency of nanoparticles was about 43%-69%. Results showed a steady release rate for nanoparticles compared to that of a pure drug powder. SEM characterization confirmed that particles were in nanosize range. DSC and XRPD results verified a decrease in drug crystallinity in the prepared formulations. In conclusion, the results of this study showed that PLGA-PEG-Praz nanoparticles could be a good choice to improve the physicochemical properties of the drug and these formulations can increase Flutamide efficacy.
Descritores: Prazosina/análise
Nanopartículas
Flutamida/uso terapêutico
-Neoplasias da Próstata/fisiopatologia
Espectroscopia de Infravermelho com Transformada de Fourier/instrumentação
Responsável: BR40.1 - DBD - Divisão de Biblioteca e Documentacão do Conjunto das Químicas


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Id: lil-741140
Autor: Nunez, Wilson Ranu Ramirez; Ozaki, Michiko Regina; Vinagre, Adriana Mendes; Collares, Edgard Ferro; Almeida, Eros Antonio de.
Título: Neural Mechanisms and Delayed Gastric Emptying of Liquid Induced Through Acute Myocardial Infarction in Rats / Mecanismos Neurais e Retardo do Esvaziamento Gástrico de Liquido Induzido no Infarto Agudo do Miocárdio em Ratos
Fonte: Arq. bras. cardiol;104(2):144-151, 02/2015. graf.
Idioma: en.
Resumo: Background: In pathological situations, such as acute myocardial infarction, disorders of motility of the proximal gut can trigger symptoms like nausea and vomiting. Acute myocardial infarction delays gastric emptying (GE) of liquid in rats. Objective: Investigate the involvement of the vagus nerve, α 1-adrenoceptors, central nervous system GABAB receptors and also participation of paraventricular nucleus (PVN) of the hypothalamus in GE and gastric compliance (GC) in infarcted rats. Methods: Wistar rats, N = 8-15 in each group, were divided as INF group and sham (SH) group and subdivided. The infarction was performed through ligation of the left anterior descending coronary artery. GC was estimated with pressure-volume curves. Vagotomy was performed by sectioning the dorsal and ventral branches. To verify the action of GABAB receptors, baclofen was injected via icv (intracerebroventricular). Intravenous prazosin was used to produce chemical sympathectomy. The lesion in the PVN of the hypothalamus was performed using a 1mA/10s electrical current and GE was determined by measuring the percentage of gastric retention (% GR) of a saline meal. Results: No significant differences were observed regarding GC between groups; vagotomy significantly reduced % GR in INF group; icv treatment with baclofen significantly reduced %GR. GABAB receptors were not conclusively involved in delaying GE; intravenous treatment with prazosin significantly reduced GR% in INF group. PVN lesion abolished the effect of myocardial infarction on GE. Conclusion: Gastric emptying of liquids induced through acute myocardial infarction in rats showed the involvement of the vagus nerve, alpha1- adrenergic receptors and PVN. .

Fundamento: Distúrbios da motilidade do intestino proximal no infarto agudo do miocárdio podem desencadear sintomas digestivos como náuseas e vômitos. O infarto do miocárdio ocasiona retardo do esvaziamento gástrico (EG) de líquido em ratos. Objetivo: Investigar se existe a influência do nervo vago (VGX), adrenoreceptores α-1, receptores GABAB do sistema nervoso central e participação do núcleo paraventricular (NPV) do hipotálamo no esvaziamento gástrico (EG) e complacência gástrica (CG) em ratos infartados. Métodos: Ratos Wistar (n = 8-15) foram divididos em: grupo infarto (INF), sham (SH) e subdivididos. O infarto foi realizado por ligadura da artéria coronária descendente anterior. A complacência gástrica foi estimada com curvas pressão-volume. Realizada vagotomia por secção dos ramos dorsal e ventral. Para verificar a ação dos receptores GABAB foi injetado baclofeno por via intra ventrículo-cerebral. Simpatectomia química foi realizada com prazosina intravenosa (iv), e na lesão do núcleo paraventricular do hipotálamo foi utilizada corrente elétrica de 1mA/10s, com esvaziamento gástrico determinado por medição da retenção gástrica (% RG) de uma refeição salina. Resultados: Não houve diferença significativa na CG. A vagotomia (VGX) reduziu significativamente a %RG; no grupo INF, o tratamento intra ventrículo-cerebral (ivc) com baclofeno reduziu significativamente a % RG; não houve conclusivamente envolvimento dos receptores GABAB em retardar o EG; o tratamento intravenoso com prazosina reduziu significativamente a %RG no grupo INF. A lesão do NPV aboliu o efeito do infarto do miocárdio no EG. Conclusão: O nervo vago, receptores α-adrenérgicos e núcleo paraventricular estão envolvidos no retardo do esvaziamento gástrico no infarto agudo do miocárdio em ratos. .
Descritores: Esvaziamento Gástrico/fisiologia
Infarto do Miocárdio/fisiopatologia
Núcleo Hipotalâmico Paraventricular/fisiopatologia
Receptores Adrenérgicos alfa 1/fisiologia
Receptores de GABA-B/fisiologia
Nervo Vago/fisiopatologia
-Antagonistas de Receptores Adrenérgicos alfa 1/farmacologia
Baclofeno/farmacologia
Agonistas dos Receptores de GABA-B/farmacologia
Gastroparesia/fisiopatologia
Infarto do Miocárdio/complicações
Prazosina/farmacologia
Ratos Wistar
Fatores de Tempo
Vagotomia
Limites: Animais
Masculino
Tipo de Publ: Research Support, Non-U.S. Gov't
Responsável: BR1.1 - BIREME


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Id: lil-699124
Autor: Tehranchi, Ali; Rezaei, Yousef; Khalkhali, Hamidreza; Rezaei, Mahdi.
Título: Effects of Terazosin and Tolterodine on Ureteral Stent Related Symptoms: A Double-Blind Placebo-Controlled Randomized Clinical Trial
Fonte: Int. braz. j. urol;39(6):832-840, Nov-Dec/2013. tab, graf.
Idioma: en.
Resumo: Objective To evaluate the effects of terazosin and tolterodine on ureteral stent discomfort. Materials and Methods Of 163 patients assessed for eligibility, 104 patients were randomly assigned to receive placebo, 2 mg of terazosin twice daily, 2 mg of tolterodine daily, or both terazosin plus tolterodine during the stenting period. Prior to stenting and at stent removal, the International Prostate Symptom Score (IPSS), the IPSS quality of life (QoL) subscore and the Visual Analog Scale for Pain were determined. The patients also reported their analgesic use during the stenting period. Results Ninety-four patients completed the study. We noted significant decreases in the total IPSS scores (p = 0.002), irritative subscore (p = 0.039), QoL (p = 0.001), flank pain (p = 0.013), voiding pain (p = 0.01) and amount of analgesics used (p = 0.02) in the groups. However, neither the obstructive subscore nor the suprapubic pain improved significantly (p = 0.251 and p = 0.522, respectively). The patients receiving terazosin plus tolterodine experienced significant reductions in the total IPSS, irritative symptoms, QoL, flank pain, voiding pain and decreased analgesics use compared with those patients receiving placebo. However, compared with placebo, terazosin monotherapy did not affect pain levels, and tolterodine monotherapy did not improve QoL, flank pain or analgesics use. Conclusions Terazosin plus tolterodine improves ureteral stent-related complications, including irritative symptoms, the amount of analgesics used, QoL, flank pain and voiding pain but does not decrease obstructive symptoms or suprapubic pain. This trial was registered at www.clinicaltrials.gov as NCT01530243. .
Descritores: Compostos Benzidrílicos/uso terapêutico
Cresóis/uso terapêutico
Fenilpropanolamina/uso terapêutico
Prazosina/análogos & derivados
Stents/efeitos adversos
Ureter/efeitos dos fármacos
Agentes Urológicos/uso terapêutico
-Método Duplo-Cego
Remoção de Dispositivo/efeitos adversos
Dor no Flanco/tratamento farmacológico
Estudos Prospectivos
Prazosina/uso terapêutico
Qualidade de Vida
Inquéritos e Questionários
Fatores de Tempo
Resultado do Tratamento
Escala Visual Analógica
Limites: Adolescente
Adulto
Feminino
Seres Humanos
Masculino
Meia-Idade
Adulto Jovem
Tipo de Publ: Ensaio Clínico Controlado Aleatório
Responsável: BR1.1 - BIREME


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Id: lil-687309
Autor: Sener, Nevzat Can; Ozturk, Ufuk; Goktug, H. N. Goksel; Gucuk, Adnan; Nalbant, Ismail; Yesil, Suleyman; Imamoglu, M. Abdurrahim.
Título: Efficacy and safety of propiverine and terazosine combination for one year in male patients with luts and detrusor overactivity
Fonte: Int. braz. j. urol;39(4):513-518, Jul-Aug/2013. tab.
Idioma: en.
Resumo: Purpose To evaluate the long term efficacy and safety of the use of propiverine and terazosine combination in patients with LUTS and DO by a placebo controlled study. Materials and Methods One hundred patients were enrolled in the study. They were randomized into two groups (each group consisted of 50 patients). Terazosine and placebo were administered to the patients in Group 1 and terazosine plus propiverine HCL was administered to Group 2. The patients were evaluated by international prostate symptom score (IPSS), the first four questions of IPSS (IPSS4), the 8th question of IPSS (quality of life-QoL), overactive bladder symptom score questionnaire (OAB-q V8), PSA test, urodynamic studies, post voiding residue (PVR). All patients were followed for one year and were reassessed for comparison. Results IPSS, IPSS4, OAB symptoms, QoL score, PVR, and Qmax scores of the groups did not differ. After one year treatment, there was significant improvement in IPSS, IPSS4, OAB symptoms, QoL and Qmax values in Group 2. No significant improvement was noted for the same parameters in Group 1. Conclusion This is the first study to show long term safety and efficacy of anticholinergic therapy for patients with LUTS. In patients with OAB or DO, long term anticholinergic treatment may be regarded as a treatment option. .
Descritores: Benzilatos/uso terapêutico
Sintomas do Trato Urinário Inferior/tratamento farmacológico
Antagonistas Muscarínicos/uso terapêutico
Prazosina/análogos & derivados
Bexiga Urinária Hiperativa/tratamento farmacológico
-Método Duplo-Cego
Quimioterapia Combinada/métodos
Prazosina/uso terapêutico
Qualidade de Vida
Inquéritos e Questionários
Fatores de Tempo
Resultado do Tratamento
Limites: Adulto
Seres Humanos
Masculino
Meia-Idade
Tipo de Publ: Ensaio Clínico Controlado Aleatório
Responsável: BR1.1 - BIREME


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Id: lil-686572
Autor: Vinagre, A.M.; Collares, E.F..
Título: Evidence for the involvement of peripheral -adrenoceptors in delayed liquid gastric emptying induced by dipyrone, 4-aminoantipyrine, and antipyrine in rats
Fonte: Braz. j. med. biol. res = Rev. bras. pesqui. méd. biol;46(9):735-738, 19/set. 2013. tab, graf.
Idioma: en.
Resumo: Dipyrone (Dp), 4-aminoantipyrine (AA), and antipyrine (At) delay liquid gastric emptying (GE) in rats. We evaluated adrenergic participation in this phenomenon in a study in male Wistar rats (250-300 g) pretreated subcutaneously with guanethidine (GUA), 100 mg·kg−1·day−1, or vehicle (V) for 2 days before experimental treatments. Other groups of animals were pretreated intravenously (iv) 15 min before treatment with V, prazosin (PRA; 1 mg/kg), yohimbine (YOH; 3 mg/kg), or propranolol (PRO; 4 mg/kg), or with intracerebroventricular (icv) administration of 25 µg PRO or V. The groups were treated iv with saline or with 240 µmol/kg Dp, AA, or At. GE was determined 10 min later by measuring the percentage of gastric retention (%GR) of saline labeled with phenol red 10 min after gavage. %GR (mean±SE, n=8) indicated that GUA abolished the effect of Dp (GUA vs V=31.7±1.6 vs 47.1±2.3%) and of At (33.2±2.3 vs 54.7±3.6%) on GE and significantly reduced the effect of AA (48.1±3.2 vs 67.2±3.1%). PRA and YOH did not modify the effect of the drugs. %GR (mean±SE, n=8) indicated that iv, but not icv, PRO abolished the effect of Dp (PRO vs V=29.1±1.7 vs 46.9±2.7%) and At (30.5±1.7 vs 49±3.2%) and significantly reduced the effect of AA (48.4±2.6 vs 59.5±3.1%). These data suggest activation of peripheral β-adrenoceptors in the delayed GE induced by phenylpyrazolone derivatives.
Descritores: Antagonistas Adrenérgicos/administração & dosagem
Ampirona/administração & dosagem
Anti-Inflamatórios não Esteroides/administração & dosagem
Antipirina/administração & dosagem
Dipirona/administração & dosagem
Esvaziamento Gástrico/efeitos dos fármacos
Receptores Adrenérgicos beta/metabolismo
-Infusões Intraventriculares
Fenolsulfonaftaleína
Prazosina/administração & dosagem
Propranolol/administração & dosagem
Ratos Wistar
Ioimbina/administração & dosagem
Limites: Animais
Masculino
Tipo de Publ: Research Support, Non-U.S. Gov't
Responsável: BR1.1 - BIREME


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Mendlowicz, Mauro Vitor
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Id: lil-656242
Autor: Pagotto, Luiz Felipe; Berger, William; Mendlowicz, Mauro Vitor; Luz, Mariana Pires; Portella, Carla Marques; Figueira, Ivan.
Título: Prazosina de liberação lenta para pacientes com transtorno do estresse pós-traumático resistentes aos ISRS / Slow-release prazosin for SSRI-resistant posttraumatic stress disorder patients
Fonte: Rev. psiquiatr. clín. (São Paulo);39(5):176-179, 2012. tab.
Idioma: pt.
Resumo: CONTEXTO: Prazosina, um antagonista de receptores alfa-1 adrenérgicos, é utilizada no tratamento de pesadelos e insônia relacionados com TEPT. Apesar das evidências sugerindo sua eficácia também no tratamento de sintomas gerais de TEPT, sua curta meia-vida (2-3 horas) pode limitar seus efeitos terapêuticos.OBJETIVO: Descrever quatro casos de pacientes com TEPT resistentes aos inibidores de recaptação de serotonina ou de serotonina e adrenalina (terapia convencional) tratados com uma apresentação de prazosina de liberação lenta.MÉTODOS: Quatro pacientes com TEPT grave, resistentes à terapia convencional, tiveram a prazosina de liberação lenta (meia-vida de 10,8 horas) adicionada as suas prescrições por pelo menos três meses. Os sintomas de TEPT foram avaliados pela PCL-C e pelos itens referentes a pesadelos e insônia da CAPS, na linha de base e no final do período de observação de cada paciente.RESULTADOS: Dois pacientes mostraram melhora dos sintomas gerais de TEPT (redução de 35,7% e 11,9% nos escores da PCL-C), e três mostraram melhora de pesadelos e insônia (nos escores da CAPS). O único paciente que recebeu doses da prazosina pela manhã e ao deitar-se foi o que mostrou a maior melhora dos sintomas gerais de TEPT.CONCLUSÃO: Possivelmente, a sustentação do bloqueio da atividade noradrenérgica no sistema nervoso central promovida pela prazosina de liberação lenta durante o dia se faz necessária para a melhora de sintomas residuais de TEPT em pacientes em tratamento convencional com antidepressivos.

BACKGROUND: Prazosin is an antagonist of alpha-1 adrenergic receptor used to treat PTSD-related nightmares and insomnia. Although evidence suggests that it is also effective in the treatment of general symptoms of PTSD, its short half-life (2-3 hours) may limit its therapeutic effects.OBJECTIVE: To describe four cases of patients with PTSD resistant to selective serotonin reuptake inhibitors (SSRIs) or selective serotonin/noradrenaline reuptake inhibitor (SNRIs) therapy (conventional therapy) treated with slow-release prazosin presentation.METHODS: Four patients with severe PTSD resistant to conventional therapy received slow-release prazosin (half-life of 10.8 hours) added to their prescription for at least three months. PTSD symptoms were evaluated by the PCL-C, together with nightmares and insomnia items of CAPS, at baseline and at the last observation of each patient.RESULTS: Two patients showed improvement in general symptoms of PTSD (reduction of 35.7% and 11.9% in PCL-C scores), and three showed relief from nightmares and insomnia (CAPS scores). The only patient who received morning and bedtime doses of prazosin showed the greatest improvement in general symptoms of PTSD.DISCUSSION: It is possible that the sustained blockade of noradrenergic activity in the central nervous system provided by slow-release prazosin during the day is necessary to further ameliorate residual PTSD symptoms in patients receiving conventional antidepressant therapy.
Descritores: Antagonistas de Receptores Adrenérgicos alfa 1
Prazosina/uso terapêutico
Transtornos de Estresse Pós-Traumáticos/terapia
Limites: Seres Humanos
Masculino
Feminino
Adulto
Responsável: BR66.1 - Divisão de Biblioteca e Documentação


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Id: lil-588992
Autor: Gurbuz, M. Cenk; Polat, Haci; Canat, Lutfi; Kilic, Mert; Caskurlu, Turhan.
Título: Efficacy of three different alpha 1-adrenergic blockers and hyoscine N-butylbromide for distal ureteral stones
Fonte: Int. braz. j. urol;37(2):195-202, Mar.-Apr. 2011. graf, tab.
Idioma: en.
Resumo: PURPOSE: To evaluate hyoscine N-butyl bromide (HBB) and three different alpha-1 blockers in the treatment of distal ureteral stones. MATERIALS AND METHODS: A total of 140 patients with stones located in the distal tract of the ureter with stone diameters of 5 to 10mm were enrolled in the present study and were randomized into 4 equal groups. Group 1 received HBB, Group 2 received alfuzosin, Group 3 received doxazosin and Group 4 received terazosin. The subjects were prescribed diclofenac injection (75 mg) intramuscularly on demand for pain relief and were followed-up after two weeks with x-rays of the kidneys, ureters, bladder and urinary ultrasonography every week. The number of pain episodes, analgesic dosage and the number of days of spontaneous passage of the calculi through the ureter were also recorded. RESULTS: The average stone size for groups 1, 2, 3 and 4 was comparable (6.13, 5.83, 5.59 and 5.48 mm respectively). Stone expulsion was observed in 11 percent, 52.9 percent, 62 percent, and 46 percent in groups 1, 2, 3 and 4 respectively. The average time to expulsion was 10.55 ± 6.21 days in group 1, 7.38 ± 5.55 days in group 2, 7.85 ± 5.11 days in group 3 and 7.45 ± 5.32 days in group 4. Alpha blockers were found to be superior to HBB (p < 0.05). CONCLUSIONS: Medical treatment of distal ureteral calculi with alfuzosin, doxazosin and terazosin resulted in a signi?cantly increased stone-expulsion rate and decreased expulsion time when compared with HBB. HBB seems to have a negative effect on stone-expulsion rate.
Descritores: Antagonistas de Receptores Adrenérgicos alfa 1/uso terapêutico
Brometo de Butilescopolamônio/uso terapêutico
Doxazossina/uso terapêutico
Prazosina/análogos & derivados
Quinazolinas/uso terapêutico
Cálculos Ureterais/tratamento farmacológico
-Estudos Prospectivos
Prazosina/uso terapêutico
Resultado do Tratamento
Limites: Adulto
Idoso
Feminino
Seres Humanos
Masculino
Meia-Idade
Tipo de Publ: Estudo Comparativo
Ensaio Clínico Controlado Aleatório
Responsável: BR1.1 - BIREME


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Id: lil-470463
Autor: Berger, William; Portella, Carla Marques; Fontenelle, Leonardo F; Kinrys, Gustavo; Mendlowicz, Mauro Vitor.
Título: Antipsicóticos, anticonvulsivantes, antiadrenérgicos e outras drogas: o que fazer quando o transtorno do estresse pós-traumático não responde aos inibidores seletivos da recaptação da serotonina? / Antipsychotics, anticonvulsants, antiadrenergics and other drugs: what to do when posttraumatic stress disorder does not respond to selective serotonin reuptake inhibitors?
Fonte: Rev. bras. psiquiatr;29(supl.2):S61-S65, out. 2007.
Idioma: en; pt.
Projeto: Conselho Nacional de Desenvolvimento Científico e Tecnológico.
Resumo: OBJETIVOS: Nesta revisão narrativa, o objetivo foi descrever as opções farmacológicas para o tratamento do transtorno de estresse pós-traumático nos casos de intolerância, resistência, refratariedade ou impossibilidade de utilizar antidepressivos, especialmente inibidores seletivos da recaptação da serotonina. MÉTODO: Consulta às bases de dados ISI Web of Science e PubMed em busca de estudos originais sobre o tratamento farmacológico do transtorno de estresse pós-traumático em diferentes cenários clínicos. RESULTADOS: Evidências preliminares apontam para a utilidade de drogas como a risperidona, a olanzapina, a lamotrigina e o prazosin como estratégias para o cenário clínico em tela. A escolha do medicamento de segunda linha deve levar em conta não só os sintomas, como também as comorbidades, os tratamentos prévios, as interações farmacológicas, os efeitos colaterais e as condições físicas do paciente. CONCLUSÕES: Futuros ensaios clínicos randomizados ainda são necessários para estabelecer com clareza alternativas farmacológicas aos antidepressivos para o tratamento do transtorno de estresse pós-traumático.

OBJECTIVES: In this narrative review, we aimed to describe different pharmacological strategies for the treatment of patients with post-traumatic stress disorder who display different levels of intolerance, resistance, refractoriness, or who are unable to take to antidepressants, especially serotonin reuptake inhibitors. METHOD: We searched the ISI web of science and the PubMed for original studies focusing in the treatment of PTSD in different clinical scenarios. RESULTS: Preliminary evidence pointed towards the efficacy of drugs such as risperidone, olanzapine, lamotrigine and prazosin as strategies to be employed in the above mentioned clinical scenarios. The choice of a specific "second line" drug should take into account not only symptoms, but also pattern of comorbidities, previous response to other treatments, pharmacological interactions, side-effects, and patient's physical conditions. CONCLUSIONS: Future randomized controlled trials should be performed in order to unveil which drugs should be prescribed in the absence of adequate treatment and response to serotonin reuptake inhibitors.
Descritores: Antagonistas Adrenérgicos/uso terapêutico
Anticonvulsivantes/uso terapêutico
Antipsicóticos/uso terapêutico
Inibidores da Captação de Serotonina/uso terapêutico
Transtornos de Estresse Pós-Traumáticos/tratamento farmacológico
-Benzodiazepinas/uso terapêutico
Prazosina/uso terapêutico
Ensaios Clínicos Controlados Aleatórios como Assunto
Risperidona/uso terapêutico
Falha de Tratamento
Triazinas/uso terapêutico
Limites: Seres Humanos
Tipo de Publ: Revisão
Responsável: BR1.1 - BIREME


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Id: lil-421364
Autor: Landa, A. I; Cabrera, R. J; Gargiulo, P. A.
Título: Prazosin blocks the glutamatergic effects of N-methyl-D-aspartic acid on lordosis behavior and luteinizing hormone secretion in the estrogen-primed female rat
Fonte: Braz. j. med. biol. res = Rev. bras. pesqui. méd. biol;39(3):365-370, Mar. 2006. graf.
Idioma: en.
Projeto: National Council of Research.
Resumo: We have observed that intracerebroventricular (icv) injection of selective N-methyl-D-aspartic acid (NMDA)-type glutamatergic receptor antagonists inhibits lordosis in ovariectomized (OVX), estrogen-primed rats receiving progesterone or luteinizing hormone-releasing hormone (LHRH). When NMDA was injected into OVX estrogen-primed rats, it induced a significant increase in lordosis. The interaction between LHRH and glutamate was previously explored by us and another groups. The noradrenergic systems have a functional role in the regulation of LHRH release. The purpose of the present study was to explore the interaction between glutamatergic and noradrenergic transmission. The action of prazosin, an alpha1- and alpha2b-noradrenergic antagonist, was studied here by injecting it icv (1.75 and 3.5 µg/6 µL) prior to NMDA administration (1 µg/2 µL) in OVX estrogen-primed Sprague-Dawley rats (240-270 g). Rats manually restrained were injected over a period of 2 min, and tested 1.5 h later. The enhancing effect induced by NMDA on the lordosis/mount ratio at high doses (67.06 ± 3.28, N = 28) when compared to saline controls (6 and 2 µL, 16.59 ± 3.20, N = 27) was abolished by prazosin administration (17.04 ± 5.52, N = 17, and 9.33 ± 3.21, N = 20, P < 0.001 for both doses). Plasma LH levels decreased significantly only with the higher dose of prazosin (1.99 ± 0.24 ng/mL, N = 18, compared to saline-NMDA effect, 5.96 ± 2.01 ng/mL, N = 13, P < 0.05). Behavioral effects seem to be more sensitive to the alpha-blockade than hormonal effects. These findings strongly suggest that the facilitatory effects of NMDA on both lordosis and LH secretion in this model are mediated by alpha-noradrenergic transmission.
Descritores: Antagonistas Adrenérgicos alfa/farmacologia
Hormônio Luteinizante/sangue
Prazosina/farmacologia
Comportamento Sexual Animal/efeitos dos fármacos
Transmissão Sináptica/efeitos dos fármacos
-Injeções Intraventriculares
Hormônio Luteinizante/efeitos dos fármacos
N-Metilaspartato/antagonistas & inibidores
Norepinefrina
Ovariectomia
Postura/fisiologia
Ratos Sprague-Dawley
Comportamento Sexual Animal/fisiologia
Limites: Animais
Feminino
Ratos
Responsável: BR1.1 - BIREME


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Id: lil-412146
Autor: Medero P, Nelson; Medero Alvarez, Nelson.
Título: Eficacia y seguridad de la terapia combinada finasteride + prazosin vs. finasteride + placebo en pacientes con hiperplasia prostática benigna / Effectiveness and security of the therapy combined finasteride + prazosin vs. finasteride + placebo in patient with hiperplasia benign prostática
Fonte: Rev. venez. urol;49(1):32-36, ene.-jun. 2003. tab.
Idioma: es.
Resumo: Se realizó un estudio doble ciego, propectivo, comparativo y controlado con placebo, con el propósito de investigar la eficacia y seguridad de la terapia concomitante de finasteride y prazosín vs. finasteride más placebo en pacientes con hiperplasia prostática beninga (HPB), sobre los síntomas de prostatismo, velocidad de flujo urinario máximo y volumen prostático. Ingresaron al estudio 20 hombres portadores de HPB. Luego de un período de tratamiento de 2 semanas con placebo, los pacientes se distribuyeron en tres grupos de medicación activa: 1A, IB, y 2. Los pacientes de los grupos 1A (n=5) y 1B (n=5) recibieron finasteride (5 mg/día) más prazosín (4mg/día); los pacintes (n=10) del grupo 2 recibieron finasteride (5 mg/día) más placebo. El primer período de tratamiento se extendió durante 24 semanas. Las siguientes 12 semanas (hasta un total de 38 semanas) los pacientes de los grupos 1B y 2 continuaron con su mismo esquema de tratamiento; en los pacientes del grupo 1A, el prazosín se sustituyó por placebo. De los 20 pacientes inicialmente incluidos, finalizaron 16. Al comparar los grupos de tratamiento, se puede apreciar cómo la terapia combinada de finasteride más prazosín produce una mejoría o reducción del puntaje total de síntomas y un incremeto en la velicidad del flujo urinario máximo que son significativamente mejores (p<0.0003 y p<0.0075, respectivamente) que la terapia de finasteride más placebo, desde el inicio del tratamiento. La medicación fue bien tolerada, y hubo una baja incidencia 10 por ciento de efectos adversos relacionados con la medicación durante el estudio. En vista de estos hallazgos, y tomando este estudio como un estudio piloto, podemos concluir que la terapia combinada de finasteride más prazosín, probablemente como consecuencia del mecanismo sinérgico entre ambos medicamentos, ofrece un ventajas en cuanto a mejoría sintomática y urodinámica, en comparación con la monoterapia, en el tratamiento de la hiperplasia prostática benigna
Descritores: Finasterida/uso terapêutico
Hiperplasia Prostática/terapia
Placebos
Prazosina
-Urologia
Venezuela
Limites: Seres Humanos
Masculino
Tipo de Publ: Estudo Comparativo
Responsável: VE1.1 - Biblioteca Humberto Garcia Arocha



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